Is atelectasis related to the development of postoperative pneumonia? a retrospective single center study.

BACKGROUND: Atelectasis may play a substantial role in the development of pneumonia. However, pneumonia has never been evaluated as an outcome of atelectasis in surgical patients. We aimed to determine whether atelectasis is related to an increased risk of postoperative pneumonia, intensive care unit (ICU) admission and hospital length of stay (LOS). METHODS: The electronic medical records of adult patients who underwent elective non-cardiothoracic surgery under general anesthesia between October 2019 and August 2020 were reviewed. They were divided into two groups: one who developed postoperative atelectasis (atelectasis group) and the other who did not (non-atelectasis group). The primary outcome was the incidence of pneumonia within 30 days after the surgery. The secondary outcomes were ICU admission rate and postoperative LOS. RESULTS: Patients in the atelectasis group were more likely to have risk factors for postoperative pneumonia including age, body mass index, a history of hypertension or diabetes mellitus and duration of surgery, compared with those in the non-atelectasis. Among 1,941 patients, 63 (3.2%) developed postoperative pneumonia; 5.1% in the atelectasis group and 2.8% in the non-atelectasis (P = 0.025). In multivariable analysis, atelectasis was associated with an increased risk of pneumonia (adjusted odds ratio, 2.33; 95% CI: 1.24 - 4.38; P = 0.008). Median postoperative LOS was significantly longer in the atelectasis group (7 [interquartile range: 5-10 days]) than in the non-atelectasis (6 [3-8] days) (P < 0.001). Adjusted median duration was also 2.19 days longer in the atelectasis group (ß, 2.19; 95% CI: 0.821 - 2.834; P < 0.001). ICU admission rate was higher in the atelectasis group (12.1% vs. 6.5%; P < 0.001), but it did not differ between the groups after adjustment for confounders (adjusted odds ratio, 1.52; 95% CI: 0.88 - 2.62; P = 0.134). CONCLUSION: Among patients undergoing elective non-cardiothoracic surgery, patients with postoperative atelectasis were associated with a 2.33-fold higher incidence of pneumonia and a longer LOS than those without atelectasis. This finding alerts the need for careful management of perioperative atelectasis to prevent or reduce the adverse events including pneumonia and the burden of hospitalizations. TRIAL REGISTRATION: None.

Head-neck movement may predispose to the development of arytenoid dislocation in the intubated patient: a 5-year retrospective single-center study.

BACKGROUND: Arytenoid dislocation is a rare laryngeal injury that may follow endotracheal intubation. We aimed to determine the incidence and risk factors for arytenoid dislocation after surgery under general anaesthesia. METHODS: We reviewed the medical records of patients who underwent operation under general anaesthesia with endotracheal intubation from January 2014 to December 2018. Patients were divided into the non-dislocation and dislocation groups depending on the presence or absence of arytenoid dislocation. Patient, anaesthetic, and surgical factors associated with arytenoid dislocation were determined using Poisson regression analysis. RESULTS: Among the 25,538 patients enrolled, 33 (0.13%) had arytenoid dislocation, with higher incidence after anterior neck and brain surgery. Patients in the dislocation group were younger (52.6 ± 14.4 vs 58.2 ± 14.2 yrs, P = 0.025), more likely to be female (78.8 vs 56.5%, P = 0.014), and more likely to be intubated by a first-year anaesthesia resident (33.3 vs 18.5%, P = 0.048) compared to those in the non-dislocation group. Patient positions during surgery were significantly different between the groups (P = 0.000). Multivariable Poisson regression identified head-neck positioning (incidence rate ratio [IRR], 3.10; 95% confidence interval [CI], 1.50-6.25, P = 0.002), endotracheal intubation by a first-year anaesthesia resident (IRR, 2.30; 95% CI, 1.07-4.64, P = 0.024), and female (IRR, 3.05; 95% CI, 1.38-7.73, P = 0.010) as risk factors for arytenoid dislocation. CONCLUSION: This study showed that the incidence of arytenoid dislocation was 0.13%, and that head-neck positioning during surgery, less anaesthetist experience, and female were significantly associated with arytenoid dislocation in patients who underwent surgeries under general anaesthesia with endotracheal intubation.

Comparison of the effect of sevoflurane or propofol anesthesia on the regional cerebral oxygen saturation in patients undergoing carotid endarterectomy: a prospective, randomized controlled study.

BACKGROUND: The monitoring of regional cerebral oxygen saturation (SrO2) using near-infrared spectroscopy is useful method to detect cerebral ischemia during. Sevoflurane and propofol decrease cerebral metabolic rate (CMRO2) in a similar manner, but the effects on the cerebral blood flow (CBF) are different. We hypothesized that the effects of sevoflurane and propofol on SrO2 were different in patients with deficits of CBF. This study compared the effect of sevoflurane and propofol on SrO2 of patients undergoing cerebral endarterectomy (CEA). METHOD: Patients undergoing CEA were randomly assigned to the sevoflurane or propofol group (n = 74). The experiment was preceded in 2 stages based on carotid artery clamping. The first stage was from induction of anaesthesia to immediately before clamping of the carotid artery, and the second stage was until the end of the operation after clamping of the carotid artery. Oxygen saturation (SrO2, SpO2), haemodynamic variables (blood pressure, heart rate), respiratory parameters (end-tidal carbon dioxide tension, inspired oxygen tension), concentration of anesthetics, and anesthesia depth (bispectral index score) were recorded. RESULTS: During stage 1 period (before carotid artery clamping), the mean value of the relative changes in SrO2 was higher (P = 0.033) and the maximal decrease in SrO2 was lower in the sevoflurane group compared with the propofol group (P = 0.019) in the contralateral (normal) site. However, there is no difference in ipsilateral site (affected site). SrO2 decreased after carotid artery clamping and increased after declamping, but the difference was not significant between two groups. Changes in mean arterial blood pressure was lower in sevoflurane group than propofol group after the carotid artery declamping (P = 0.048). CONCLUSION: Propofol-remifentanil anesthesia was comparable with sevoflurane-remifentanil anesthesia in an aspect of preserving the SrO2 in patients undergoing carotid endarterectomy. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02609087 , retrospectively registered on November 18, 2015.

Background anaesthetic agents do not influence the impact of arginine vasopressin on haemodynamic states and cerebral oxygenation during shoulder surgery in the beach chair position: a prospective, single-blind study.

BACKGROUND: Administration of arginine vasopressin (AVP) is associated with reducing jugular venous (SjvO2) and regional cerebral (rScO2) oxygen saturation under propofol-remifentanil (P/R) anaesthesia. We determined whether background anaesthetics modulate the effect of AVP on cerebral oxygenation and haemodynamics. METHODS: We randomly allocated 60 adult patients scheduled for shoulder surgery in the beach chair position (BCP) into 4 groups, to receive either an intravenous bolus of saline (groups PR-S and SN-S) or 0.05 U/kg AVP (groups PR-AVP and SN-AVP) under P/R or sevoflurane-nitrous oxide (S/N) anaesthesia (n = 15 each). Haemodynamic variables, SjvO2 and rScO2 were measured. RESULTS: AVP significantly increased mean arterial blood pressure (MAP) and decreased rScO2 in either anaesthetic group. AVP also decreased SjvO2 in the P/R groups but not in the S/N groups. The AVP-treated groups showed higher MAP and cerebral desaturation (>20% rScO2 decrease from baseline), along with lower HR and rScO2 in the BCP than those in the saline-treated groups. In contrast, AVP did not affect SjvO2 values or the incidence of SjvO 2  < 50%. Baseline SjvO2 was lower and the magnitude of its reduction in the BCP was greater in the PR-AVP group than in the SN-AVP group, and the lowest SjvO2 values were 37 ± 6 and 57 ± 8%, respectively (P < 0.001). CONCLUSIONS: The choice of anaesthetic regimen did not affect cerebral oxygenation or haemodynamics of AVP in the BCP. However, the negative effect of AVP on cerebral oxygenation should be considered, especially under P/R anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01687894 , registered on September 18, 2012.

Population pharmacokinetics of ramosetron.

Ramosetron is a selective serotonergic 5-hydroxy-tryptamine receptor 3 antagonist that is used to prevent and treat postoperative nausea and vomiting. This study aimed to characterize the population pharmacokinetics of ramosetron in patients undergoing surgery with general anesthesia. Patients aged 19-80 years received a single intravenous bolus of ramosetron (0.3, 0.45, or 0.6 mg) 30 min before the end of surgery. Blood samples were collected, and plasma concentrations of ramosetron were measured by high performance liquid chromatography-tandem mass spectrometry. Pooled data from 50 patients and 479 pharmacokinetic samples were used for population pharmacokinetic analysis using the nonlinear mixed effect modeling program (NONMEM(®)). The pharmacokinetics of ramosetron was best described by a three-compartment mammillary model with first-order elimination. Based on allometric principles, body weight was incorporated in the base model, along with fixed allometric exponents. The typical value of clearance was 0.19 L/h in a 60-kg subject, and it decreased approximately 3% for every year of age, starting at age of 57. The bootstrap method and visual predictive check showed that the final pharmacokinetic model was appropriate. A population pharmacokinetic model of ramosetron was constructed in adult surgical patients, providing a foundation for further defining the relationship between ramosetron dose and postoperative nausea and vomiting.

Protective effect of sauchinone against regional myocardial ischemia/reperfusion injury: inhibition of p38 MAPK and JNK death signaling pathways.

Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3ß was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% ± 5.3% in the sauchinone group vs 44.4% ± 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3ß was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.

Sugammadex is associated with shorter hospital length of stay after open lobectomy for lung cancer: a retrospective observational study.

BACKGROUND: Sugammadex is associated with few postoperative complications. Postoperative pulmonary complications (PPC) are related to prolonged hospitalizations. Present study explored whether the use of sugammadex could reduce PPCs and thereby reduce hospital length of stay (LOS) after lung surgery. METHODS: We reviewed the medical records of patients who underwent elective open lobectomy for lung cancer from January 2010 to December 2015. Patients were divided into the sugammadex group and pyridostigmine group. The primary outcome was hospital LOS and secondary outcomes were postoperative complications and overall survival at 1 year. The cohort was subdivided into patients with and without prolonged LOS to explore the effects of sugammadex on outcomes in each group. Risk factors for LOS were determined via multivariate analyses. After propensity score matching, 127 patients were assigned to each group. RESULTS: Median hospital LOS was shorter (10.0 vs. 12.0 days) and the incidence of postoperative atelectasis was lower (18.1 vs. 29.9%) in the sugammadex group. However, no significant difference in overall survival between the groups was seen over 1 year (hazard ratio, 0.967; 95% confidence interval, 0.363 to 2.577). Sugammadex was a predictor related to LOS (exponential coefficient 0.88; 95% CI 0.82-0.95). CONCLUSIONS: Our data suggest that sugammadex is a preferable agent for neuromuscular blockade (NMB) reversal than cholinesterase inhibitors in this patient population. TRIAL REGISTRATION: This study registered in the Clinical Research Information Service of the Korea National Institute of Health (approval number: KCT0004735 , Date of registration: 21 January 2020, Retrospectively registered).

Effects of high versus low inspiratory oxygen fraction on postoperative clinical outcomes in patients undergoing surgery under general anesthesia: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To determine whether high perioperative inspired oxygen fraction (FiO2) compared with low FiO2 has more deleterious postoperative clinical outcomes in patients undergoing non-thoracic surgery under general anesthesia. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Operating room, postoperative recovery room and surgical ward. PATIENTS: Surgical patients under general anesthesia. INTERVENTION: High perioperative FiO2 (≥0.8) vs. low FiO2 (≤0.5). MEASUREMENTS: The primary outcome was mortality within 30 days. Secondary outcomes were pulmonary outcomes (atelectasis, pneumonia, respiratory failure, postoperative pulmonary complications [PPCs], and postoperative oxygen parameters), intensive care unit (ICU) admissions, and length of hospital stay. A subgroup analysis was performed to explore the treatment effect by body mass index (BMI). MAIN RESULTS: Twenty-six trials with a total 4991 patients were studied. The mortality in the high FiO2 group did not differ from that in the low FiO2 group (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.42-1.97, P = 0.810). Nor were there any significant differences between the groups in such outcomes as pneumonia (RR 1.19, 95% CI 0.74-1.92, P = 0.470), respiratory failure (RR 1.29, 95% CI 0.82-2.04, P = 0.270), PPCs (RR 1.05, 95% CI 0.69-1.59, P = 0.830), ICU admission (RR 0.94, 95% CI 0.55-1.60, P = 0.810), and length of hospital stay (mean difference [MD] 0.27 d, 95% CI -0.28-0.81, P = 0.340). The high FiO2 was associated with postoperative atelectasis more often (risk ratio 1.27, 95% CI 1.00-1.62, P = 0.050), and lower postoperative arterial partial oxygen pressure (MD -5.03 mmHg, 95% CI -7.90- -2.16, P < 0.001). In subgroup analysis of BMI >30 kg/m2, these parameters were similarly affected between the groups. CONCLUSIONS: The use of high FiO2 compared to low FiO2 did not affect the short-term mortality, although it may increase the incidence of atelectasis in adult, non-thoracic patients undergoing surgical procedures. Nor were there any significant differences in other secondary outcomes.

Fluid management in perioperative and critically ill patients.

Fluid therapy to restore and/or maintain tissue perfusion may affect patient outcomes in perioperative, emergency, and intensive care. Kinetic analyses and outcome-oriented studies have provided more insight into fluid management. Crystalloids are slowly distributed to the interstitial space, and the efficiency (proportion of infused fluid retained in the bloodstream) is 50%-75% as long as infusion continues and may increase up to 100% when the arterial pressure has decreased. Elimination of the infused fluid during general anesthesia and surgery is very slow, amounting to only 10%-20% compared with that in conscious patients. When the endothelial glycocalyx layer is degraded in sepsis or trauma-induced systemic inflammation, turnover of colloids and crystalloids is accelerated and the efficiency is reduced, which may lead to tissue edema, inflammation, poor wound healing, and organ dysfunction. Balanced crystalloids are pragmatic initial resuscitation fluids and improve patient outcomes compared to saline (0.9% sodium chloride). Albumin may be beneficial, but other synthetic colloids appear to increase the risk of acute kidney injury and death among patients in the intensive care unit. Fluid kinetics is likely to change based on patient physiological conditions (e.g., general anesthesia, surgery, stress, dehydration, blood pressure, or inflammation) and fluid types. To maximize efficacy and minimize iatrogenic side effects, fluids should be prescribed based on individual patient factors, disease states, and other treatment remedies.

Role of vasopressin in current anesthetic practice.

Arginine vasopressin (AVP), also known as antidiuretic hormone, is a peptide endogenously secreted by the posterior pituitary in response to hyperosmolar plasma or systemic hypoperfusion states. When administered intravenously, it causes an intense peripheral vasoconstriction through stimulation of V1 receptors on the vascular smooth muscle. Patients in refractory shock associated with severe sepsis, cardiogenic or vasodilatory shock, or cardiopulmonary bypass have inappropriately low plasma levels of AVP ('relative vasopressin deficiency') and supersensitivity to exogenously-administered AVP. Low doses of AVP and its synthetic analog terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in the treatment of refractory arterial hypotension in patients chronically treated with renin-angiotensin system inhibitors, cardiac arrest, or bleeding esophageal varices. In the perioperative setting, they represent attractive adjunct vasopressors in advanced shock states that are unresponsive to conventional therapeutic strategies.

Antinociceptive effects and synergistic interaction with morphine of intrathecal metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats.

Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved in the modulation of nociception. While the antinociceptive effects of the mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less clear. This study investigated the effects of an intrathecal mGluR2/3 agonist, APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the formalin test and thermal stimulation test. We also examined their interaction with intrathecal morphine for the antinociceptive effect. APDC had little effect on the formalin-induced nociception. In contrast, LY341495 caused a dose-dependent suppression of the phase 2 flinching response to the formalin stimulus without affecting phase 1 flinching response. Furthermore, the suppression of pain behavior by LY341495 during phase 2 was reduced significantly by pretreatment with APDC. LY341495 and morphine also showed synergistic drug interaction for antinociception during phase 2 in the formalin test.

In vivo bioluminescence imaging of cord blood derived mesenchymal stem cell transplantation into rat myocardium.

OBJECTIVE: The conventional method for the analysis of myocardial cell transplantation depends on postmortem histology. Here, we have sought to demonstrate the feasibility of a longitudinal monitoring of transplanted cell survival in living animals, accomplished with optical imaging techniques and pharmacological interventions. METHODS: Human cord blood (50 ml) was donated with parental consent. After getting cord blood derived mesenchymal stem cells (CBMSCs), cells were transfected (MOI = 100) overnight with adenovirus encoding firefly luciferase gene (Ad-CMV-Fluc). Our experimental Sprague-Dawley rats (n = 12) were given intramyocardial injections containing 1 x 10(6) CBMSCs, which had been made to express the firefly luciferase (Fluc) reporter gene. Optical bioluminescence imaging was then conducted using a cooled charged-coupled device (CCD) camera (Xenogen), beginning on the day after the transplantation (day 1). Groups of mice were intraperitoneally injected with cyclosporine (5 mg/kg) or tacrolimus (1 mg/kg), in an attempt to determine the degree to which cell survival had been prolonged, and these values were then compared with the cell survival values of the negative control group. The presence of transplanted CBMSCs on in vivo images confirmed by in situ hybridization for human specific Alu in the myocardium. RESULTS: Cardiac bioluminescence signals were determined to be present for 6 days after transplantation: day 1 (97000 +/- 9100 x 10(5) p/s/cm2/sr), day 3 (9600 +/- 1110 p/s/cm2/sr), and day 5 (3200 +/- 550 p/s/cm2/sr). The six mice that received either cyclosporine or tacrolimus displayed cardiac bioluminescence signals for a period of 8 days after transplantation. We observed significant differences between the treated group and the non-treated group, beginning on day 3 (tacrolimus; 26500 +/- 4340 p/s/cm2/sr, cyclosporine; 27200 +/- 3340 p/s/cm2/sr, non-treated; 9630 +/- 1180 p/s/cm2/sr, p < 0.01), and persisting until day 7 (tacrolimus; 12500 +/- 2946 p/s/cm2/sr, cyclosporine; 7310 +/- 1258 p/s/cm2/sr, non-treated; 2460 +/- 160 p/s/cm2/sr, p < 0.01). The human-derived CBMSCs were detected in the myocardium 3 days after transplantation by in situ hybridization. CONCLUSIONS: The locations, magnitude, and survival duration of the CBMSCs were noninvasively monitored with a bioluminescence optical imaging system. We determined that optical molecular imaging expedites the fast throughput screening of pharmaceutical agents, allowing for the noninvasive tracking of cell survival within animals. In rat cardiac CBMSC transplant models, transient immunosuppressive treatment with tacrolimus or cyclosporine was shown to improve donor cell survival.

Relevance of radiological and clinical measurements in predicting difficult intubation using light wand (Surch-lite™) in adult patients.

OBJECTIVE: To determine the correlation between anatomical features of the upper airway (evaluated via computed tomography imaging) and the ease of light wand-assisted endotracheal intubation in patients undergoing ear, nose and throat surgery under general anaesthesia. METHODS: Mallampati class, laryngoscopic grade, thyromental distance, neck circumference, body mass index, mouth opening and upper lip bite class were assessed. Epiglottis length and angle, tongue size and narrowest pharyngeal distance were determined using computed tomography imaging. Intubation success rate, time to successful intubation (intubating time) and postoperative throat symptoms were documented. RESULTS: Of 152 patients, 148 (97.4%) were successfully intubated on the first attempt (mean intubating time 11.5 ± 6.7 s). Intubating time was positively correlated with laryngoscopic grade and body mass index in both male and female patients, and Mallampati class and neck circumference in male patients. Epiglottis length was positively correlated with intubating time. CONCLUSIONS: Ease of intubation was influenced by epiglottis length. Radiological evaluation may be useful for preoperative assessment of patients undergoing endotracheal intubation with light wand.

Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test.

Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.

Vasopressin ameliorates hypotension induced by beach chair positioning in a dose-dependent manner in patients undergoing arthroscopic shoulder surgery under general anesthesia.

BACKGROUND: The beach chair position (BCP) is associated with hypotension that may lead to cerebral ischemia. Arginine vasopressin (AVP), a potent vasoconstrictor, has been shown to prevent hypotension in BCP. It also improves cerebral oxygenation in different animal models. The present study examined the effect of escalating doses of AVP on systemic hemodynamics and cerebral oxygenation during surgery in BCP under general anesthesia. METHODS: Sixty patients undergoing arthroscopic shoulder surgery in BCP under general anesthesia were randomly allocated to receive either saline (control, n = 15) or three different doses of AVP (0.025, 0.05, or 0.075 U/kg; n = 15 each) 2 minutes before BCP. Mean arterial pressure (MAP), heart rate (HR), regional cerebral oxygen saturation (SctO2), and jugular venous oxygen saturation (SjvO2) were measured after induction of anesthesia and before (presitting in supine position) and after BCP. RESULTS: AVP per se given before BCP increased MAP, and decreased SjvO2, SctO2, and HR in all patients (P < 0.05 for all). BCP decreased MAP, the magnitude of which and hence the incidence of hypotension was decreased by AVP in a dose-dependent manner. While in BCP, every dose of AVP reduced the HR and SctO2. Accordingly, it increased the incidence of cerebral desaturation (> 20% SctO2 decrease from the baseline value) with no differences in SjvO2 and the incidence of SjvO2 < 50% or SjvO2 < 40% among the groups. CONCLUSIONS: AVP ameliorates hypotension associated with BCP in a dose-dependent manner in patients undergoing shoulder surgery under general anesthesia. However, AVP may have negative effects on SctO2 before and after BCP and on SjvO2 before BCP.

Effects of intravenously administered indocyanine green on near-infrared cerebral oximetry and pulse oximetry readings.

BACKGROUND: Intravenously administered indocyanine green (ICG) may cause misreadings of cerebral oximetry and pulse oximetry in patients undergoing carotid endarterectomy under general anesthesia. The present study determined the effects of two different doses (12.5 mg vs. 25 mg) of ICG on regional cerebral tissue oxygen saturation (SctO2) and percutaneous peripheral oxygen saturation (SpO2). METHODS: Twenty-six patients receiving ICG for videoangiography were divided into two groups according to the dosage (12.5 mg and 25 mg, n = 13 in each group). Heart rate, arterial blood pressure, SctO2, and SpO2 were measured before and after an intravenous bolus administration of ICG. RESULTS: Following the dye administration, no changes in heart rate or arterial blood pressure were noted in either group. SctO2 was increased in both groups; however, the magnitude of the increase was greater (21.6 ± 5.8% vs. 12.6 ± 4.1%, P < 0.0001) and more prolonged (28.4 ± 9.6 min vs. 13.8 ± 5.2 min, P < 0.0001) in the 25 mg group than in the 12.5 mg group. In contrast, SpO2 was decreased in both groups; the magnitude of the decrease was greater in the 25 mg group than in the 12.5 mg group (4.0 ± 0.8% vs. 1.6 ± 1.0%, P < 0.0001). There were no differences in the time to reach the peak SctO2 or to reach the nadir SpO2 between the two groups. CONCLUSIONS: In patients given ICG for videoangiography, a 25 mg bolus results in a greater and more prolonged increase in SctO2 and a greater reduction in SpO2 than a 12.5 mg bolus, with no differences in the time to reach the peak SctO2 or to reach the nadir SpO2.

Epigallocatechin-3-gallate, a green tea catechin, protects the heart against regional ischemia-reperfusion injuries through activation of RISK survival pathways in rats.

Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has been shown to modulate numerous molecular targets in the setting of inflammation. This study aimed to determine whether EGCG protects against regional myocardial ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2) and GSK-3ß or apoptotic kinases (p38 and JNK). The rats were subjected to I/R injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10 mg/kg, intravenously) was administered alone or along with wortmannin (PI3K inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion. Wortmannin was administered 10 min before the reperfusion. Infarct size was measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3ß, and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after 10 min of reperfusion. EGCG reduced the infarct size compared with the control (25.4 ± 9.2 versus 43.2 ± 8.2 %, p < 0.05). Wortmannin alone did not affect the infarct size, but abolished the EGCG-induced infarct size limiting effect, indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG significantly enhanced the phosphorylation of Akt and GSK-3ß but not ERK1/2, while it reduced that of p38 and JNK. These results suggest that EGCG has a protective effect against regional myocardial I/R injuries through activation of the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective effects in patients undergoing surgeries prone to myocardial I/R injuries.

Anesthetic requirements and stress hormone responses in chronic spinal cord-injured patients undergoing surgery below the level of injury: nitrous oxide vs remifentanil.

BACKGROUND: Nitrous oxide (N2O) and remifentanil both have anesthetic-reducing and antinociceptive effects. We aimed to determine the anesthetic requirements and stress hormone responses in spinal cord-injured (SCI) patients undergoing surgery under sevoflurane anesthesia with or without pharmacodynamically equivalent doses of N2O or remifentanil. METHODS: Forty-five chronic, complete SCI patients undergoing surgery below the level of injury were randomly allocated to receive sevoflurane alone (control, n = 15), or in combination with 67% N2O (n = 15) or target-controlled infusion of 1.37 ng/ml remifentanil (n = 15). Sevoflurane concentrations were titrated to maintain a Bispectral Index (BIS) value between 40 and 50. Measurements included end-tidal sevoflurane concentrations, mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine and cortisol concentrations. RESULTS: During surgery, MAP, HR, and BIS did not differ among the groups. Sevoflurane concentrations were lower in the N2O group (0.94 ± 0.30%) and the remifentanil group (1.06 ± 0.29%) than in the control group (1.55 ± 0.34%) (P < 0.001, both). Plasma concentrations of norepinephrine remained unchanged compared to baseline values in each group, with no significant differences among groups throughout the study. Cortisol levels decreased during surgery as compared to baseline values, and returned to levels higher than baseline at 1 h after surgery (P < 0.05) without inter-group differences. CONCLUSIONS: Remifentanil (1.37 ng/ml) and N2O (67%) reduced the sevoflurane requirements similarly by 31-39%, with no significant differences in hemodynamic and neuroendocrine responses. Either remifentanil or N2O can be used as an anesthetic adjuvant during sevoflurane anesthesia in SCI patients undergoing surgery below the level of injury.

Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3ß and inhibition of p38 MAPK and JNK.

BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases. METHODS: Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3ß]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3ß, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion. RESULTS: Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3ß, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3ß induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3ß compared with the control. CONCLUSIONS: Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3ß, and attenuation of p38 and JNK.

Neuroprotective effects of remifentanil against transient focal cerebral ischemia in rats.

BACKGROUND: Opioid agonists have been implicated in neuroprotection from hypoxic injury through regulating mitogen-activated protein kinases and cytokines. We determined the effects of remifentanil in focal brain ischemia and reperfusion (I/R) injury. Mechanisms linked to mitogen-activated protein kinases, including extracellular signaling-regulated kinase (ERK) 1/2, p38 kinases, and c-Jun N-terminal kinase (JNK), and various cytokines were also examined. METHODS: Male Sprague-Dawley rats were subjected to an I/R insult consisting of 90 minutes' middle cerebral artery occlusion (MCAO) followed by reperfusion under general anesthesia. Neurological deficit scores and infarct volume were determined after 24 hours of reperfusion. Remifentanil (5 µg/kg/min) was given alone or combined with naltrindole (δ-opioid receptor antagonist; 1 mg/kg), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (µ-opioid receptor antagonist; 1 mg/kg), or 5'-guanidinonaltrindole (κ-opioid receptor antagonist; 1 mg/kg). Opioid antagonists were administered 20 minutes before MCAO. Remifentanil infusion was started 10 minutes before MCAO and continued throughout. The control group was without drugs. The expression levels of ERK1/2, p38, and JNK, and also those of tumor necrosis factor-α (TNF-α) and interleukin-6, were determined after 1, 3, and 24 hours of reperfusion. RESULTS: Remifentanil significantly improved the functional outcome and reduced the infarct volumes (69.0±24.3 mm(3) vs. 108.9±24.8 mm(3)), which were not affected by D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) or 5'-guanidinonaltrindole, but were abolished by naltrindole. The I/R insult enhanced the phosphorylation of ERK 1/2 and the expression of TNF-α, which were significantly reduced by remifentanil. Neither the phosphorylation of p38 and JNK nor the production of interleukin-6 was altered throughout the experiment. CONCLUSIONS: Remifentanil may be neuroprotective against focal I/R injury, possibly through the activation of δ-opioid receptors and attenuation of ERK 1/2 activity and TNF-α production, in the rat brain.